Levetiracetam Protects Spinal Motor Neurons Against Glutamate-Induced Neurotoxicity in Culture

Abstract

Background: Levetiracetam is widely used in numerous patients with epileptic seizures. In an animal model of cerebral ischemia after the occlusion of the internal carotid artery, pre-treatment with levetiracetam could reduce the infarct size. However, little is known how this antiepileptic drug can act on motor neurons. The purpose of this study is to evaluate whether levetiracetam has neuroprotective effects on spinal motor neurons in glutamate-treated culture of neonatal rats. 

Methods: Postnatal organotypic spinal cord cultures were exposed to glutamate (10^-5 M) alone or glutamate (10^-5 M) plus levetiracetam (10^-5, 10^-6 and 10^-7 M). Cultures were treated for two weeks and morphological changes were examined. The number of surviving spinal motor neurons and the activities of choline acetyltransferase (ChAT) were measured. 

Results: Cultures treated with glutamate had significant reductions of the surviving motor neurons and the ChAT activities compared to non-glutamate-treated control culture. Cultures added both glutamate and levetiracetam showed significantly suppression of the neuronal loss and potentiation of the ChAT activities. 

Conclusions: The present study indicated that levetiracetam prolonged the survival and the function of spinal motor neurons against glutamate-induced neurotoxicity in culture. This drug may have a therapeutic potential for several diseases that kill or degenerate the spinal motor neurons, including spinal cord injury and amyotrophic lateral sclerosis.




doi:10.4021/jnr89w